Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a breast cancer (...) predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Margaret Cavendish's prolific and wide-ranging contributions to seventeenth-century intellectual culture are impossible to contain within the discrete confines of modern academic disciplines. Paying attention to the innovative uses of genre through which she enhanced and complicated her writings both within literature and beyond, this collection addresses her oeuvre and offers the most comprehensive and multidisciplinary resource on Cavendish's works to date. The astonishing breadth of her varied intellectual achievements is reflected through elegantly arranged sections on History of Science, Philosophy, Literature, (...) Politics and Reception, and New Directions, together with an Afterword by award-winning novelist Siri Hustvedt. The first book to cover nearly all of Cavendish's major works in a single volume, this collection brings together a variety of expert perspectives to illuminate the remarkable ideas and achievements of one of the most fascinating and prolific figures of the early modern period. (shrink)

This book compares two competing theories of human nature: the more traditional theory espoused in different forms by centuries of western philosophy and the newer, Darwinian model. In the traditional view, the human being is a hybrid being, with a lower, animal nature and a higher, rational or “spiritual” component. The competing Darwinian account does away with the idea of a higher nature and attempts to provide a complete reduction of human nature to the evolutionary goals of survival and reproduction. (...) Whitley Kaufman presents the case that the traditional conception, regardless of one's religious views or other beliefs, provides a superior account of human nature and culture. We are animals, but we are also rational animals. Kaufman explores the most fundamental philosophical questions as they relate to this debate over human nature—for example: Is free will an illusion? Is morality a product of evolution, with no objective basis? Is reason merely a tool for promoting reproductive success? Is art an adaptation for attracting mates? Is there any higher meaning or purpose to human life? Human Nature and the Limits of Darwinism aims to assess the competing views of human nature and present a clear account of the issues on this most pressing of questions. It engages in a close analysis of the numerous recent attempts to explain all human aims in terms of Darwinian processes and presents the arguments in support of the traditional conception of human nature. (shrink)

The doctrine of karma and rebirth is often praised for its ability to offer a successful solution to the Problem of Evil. This essay evaluates such a claim by considering whether the doctrine can function as a systematic theodicy, as an explanation of all human suffering in terms of wrongs done in either this or past lives. This purported answer to the Problem of Evil must face a series of objections, including the problem of anylackofmemoryofpastlives,the lack of proportionality between wrongdoing (...) and the observed suffering in the world, the problem of infinite regress of explanation, and the problem of compatibility of free will with karmic determinism. These objections, either separately or taken together, provide (it is argued) sufficient reason to doubt whether the doctrine of karma and rebirth can in fact provide a satisfactory theodicy. (shrink)

It is widely held by moral philosophers that J.J. Thomson’s “Loop Variant,” a version of the Trolley Problem first presented by her in 1985, decisively refutes the Doctrine of Double Effect as the right explanation of our moral intuitions in the various trolley-type cases.See Bruers and Brackman, “A Review and Systematization of the Trolley Problem,” Philosophia 42:2 : 251–269; T. Scanlon, Moral Dimensions: Permissibility, Meaning, Blame ; Peter Singer, “Ethics and Intuitions,” Journal of Ethics 9:314 : 331–352, p. 340; Matthew (...) Liao, “The Loop Case and Kamm’s Doctrine of Triple Effect,” Philosophical Studies 146:2 : 223–231; H. Sauer, “Morally Irrelevant Factors: What’s Left of the Dual Process Model of Moral Cognition?,” Philosophical Psychology 25:6 : 783–811, p. 797. Frances Kamm suggests the DDE can be saved from the objection, but only by radically revising it into a doctrine of “Triple Effect” (In .. (shrink)

The problem of punishment -- Punishment as crime prevention -- Can retributive punishment be justified? -- The mixed theory of punishment -- Retribution and revenge -- What is the purpose of retribution? -- Making sense of honor -- Is punishment justified?

In Justified Killing, Whitley R. P. Kaufman argues that none of the leading theories adequately explains why it is permissible even to kill an innocent attacker in self-defense, given the basic moral prohibition against killing the innocent. Kaufman suggests that such an explanation can be found in the traditional Doctrine of Double Effect, according to which self-defense is justified because the intention of the defender is to protect himself rather than harm the attacker.

The doctrine of karma and rebirth is often praised for its ability to offer a successful solution to the Problem of Evil. This essay evaluates such a claim by considering whether the doctrine can function as a systematic theodicy, as an explanation of all human suffering in terms of wrongs done in either this or past lives. This purported answer to the Problem of Evil must face a series of objections, including the problem of any lack of memory of past (...) lives, the lack of proportionality between wrongdoing and the observed suffering in the world, the problem of infinite regress of explanation, and the problem of compatibility of free will with karmic determinism. These objections, either separately or taken together, provide (it is argued) sufficient reason to doubt whether the doctrine of karma and rebirth can in fact provide a satisfactory theodicy. (shrink)

The vast network of Drosophila geneticists spawned by Thomas Hunt Morgan's fly room in the early 20th century has justifiably received a significant amount of scholarly attention. However, most accounts of the history of Drosophila genetics focus heavily on the "boss and the boys," rather than the many other laboratory groups which also included large numbers of women. Using demographic information extracted from the Drosophila Information Service directories from 1934 to 1970, we offer a profile of the gendered division of (...) labor within Drosophila genetics in the United States during the middle decades of the 20th century. Our analysis of the gendered division of labor supports a reconsideration of laboratory practices as different forms of work. (shrink)

In a recent edition of the journal Philosophy, Sophie Botros asserts that modern ethical theorists have badly misunderstood the role of the Doctrine of Double Effect, turning it into a device by which to prohibit actions which are deemed impermissible; whereas the true function of the Doctrine is rather one of justifying actions. In my reply, I argue that Dr Botros has misunderstood the Doctrine: that its ‘prohibitive’ and its ‘justificatory’ roles are merely two sides of the same coin, since (...) its function is to decide for a given action whether it is permissible or impermissible. Furthermore, Dr Botros has misconstrued the essential contribution of the DDE is not the balancing of good results against bad ones, but the quite different position that the crucial moral distinction is between intended and merely foreseen results. (shrink)

It is an assumption widely shared by both retributivists and anti-retributivists that revenge is a morally impermissible basis for inflicting harm. Retributivists have thus exercised great ingenuity in demonstrating that retribution is fundamentally different from revenge. But this is, I argue, to misconstrue the problem. The problem is rather to recognize the essential continuity between revenge and retribution, and to address the question whether there is a moral basis for the very idea of inflicting harm in response to moral wrongdoing. (...) I argue that the only plausible such moral justification is the defense of honor, and that the debate needs to be focused on the legitimacy of honor as a moral basis for punishment. (shrink)

Sam Harris’ new book “The Moral Landscape” is the latest in a series of attempts to provide a new “science of morality.” This essay argues that such a project is unlikely to succeed, using Harris’ text as an example of the major philosophical problems that would be faced by any such theory. In particular, I argue that those trying to construct a scientific ethics need pay far more attention to the tradition of moral philosophy, rather than assuming the debate is (...) simply between a scientific ethics and a “supernatural” ethics provided by religion. (shrink)

A frequent argument is that Darwin’s theory of evolution has or should revolutionize our conception of the relation between humans and animals, though society has yet to take account of that revolution in our treatment of animals. On this view, after Darwin demonstrated the essential continuity of humans and animals, traditional morality must be rejected as speciesist in seeing humans as fundamentally distinct from other animals. In fact, the argument is of dubious merit. While there is plenty of room for (...) improving our treatment of animals, it is unlikely that these shortcomings can be blamed on scientific ignorance, or that knowledge of the theory of evolution has any clear moral implications for our treatment of animals. (shrink)

Introduction -- The principles of self-defense -- The leading theories of self-defense -- The doctrine of double effect -- Double effect and common sense morality -- Can double effect justify self-defense? -- Conclusion: Justifying self-defense.

In this essay I analyze and defend the common sense moral conviction that terrorism, i.e., the use of violence against civilians for political or military purposes, is always morally impermissible. Terrorism violates the fundamental moral prohibition against harming the innocent, even to produce greater overall good. It is therefore just the sort of case that serves as a refutation of consequentialist moral theories. From a deontological perspective, the only remotely plausible forms of justification for a terrorist act would be that (...) it constitutes a form of justifiable punishment of the guilty, or that it is legitimate self-defense against an aggressor. But an examination of the fundamental moral and legal principles of punishment and self-defense demonstrates that neither of these claims can succeed. Since terrorism cannot be justified either as punishment or as self-defense, it cannot be morally justified at all. (shrink)

In this essay I analyze and defend the common sense moral conviction that terrorism, i.e., the use of violence against civilians for political or military purposes, is always morally impermissible. Terrorism violates the fundamental moral prohibition against harming the innocent, even to produce greater overall good. It is therefore just the sort of case that serves as a refutation of consequentialist moral theories. From a deontological perspective, the only remotely plausible forms of justification for a terrorist act would be that (...) it constitutes a form of justifiable punishment of the guilty, or that it is legitimate self-defense against an aggressor. But an examination of the fundamental moral and legal principles of punishment and self-defense demonstrates that neither of these claims can succeed. Since terrorism cannot be justified either as punishment or as self-defense, it cannot be morally justified at all. (shrink)

Background: Clinical research nurses experience unique challenges in the context of their role that can lead to conflict and moral distress. Although examined in many areas, moral distress has not been studied in clinical research nurses. Research aim: The aim of this study was to examine moral distress in clinical research nurses and the relationship between moral distress scores and demographic characteristics of clinical research nurses. Research design: This was a descriptive quantitative study to measure moral distress in clinical research (...) nurses using the Measure of Moral Distress – Healthcare Professionals (MMD-HP) administered electronically. Demographic data were also collected. Participants and research context: Registered nurses working in the clinical research nurse role ( N = 322) were recruited through use of social media, emails, digital flyers, and snowball recruitment. Data was analyzed using SPSS. Pearson’s correlation, independent t-test, and one-way ANOVA were performed to explore differences among the demographic variables. Ethical considerations: This study was approved by the Institutional Review Board at Texas Woman’s University. A consent statement was included, and completion of the questionnaire was construed as consent. Findings/results: Analysis revealed a mean overall moral distress score of 79.58 (SD = 64.27) and median of 67, with a range of 0–354. Moral distress scores were negatively correlated with clinical research nurse age ( r = 0-.156, p < 0.05). Reliability of the MMD-HP was demonstrated with a Cronbach’s alpha of 0.93. Conclusions: The findings demonstrate that clinical research nurses do experience moral distress and revealed a wide range of scores. Further research is necessary to determine potential patient impact due to moral distress and to develop processes to minimize moral distress in the clinical research setting. This study was conducted during the COVID-19 pandemic, and the digital recruitment methods proved effective in recruiting a wide range of clinical research nurses, both nationally and internationally. (shrink)

Excerpt from Uebersicht ber das Aristotelische Lehrgeb ude und Er rterung der Lehren Seiner N chsten Nachfolger: Als Uebergang zur Dritten Entwickelungsperiode der Griechischen Philosophie Sci) bergebe hie $erbattnifie 111e cbe hie @d einnng biefe8 %anbe8 meiner (R)efcbicbte n1eljr brei Sabre lang ber3ogert haben; bie @1'm bnnng befiel en m rbe mir fcbn1er3; I11I) unb fiir ben 8efer ohne 8'nterefie fein. S'huen finh fie befannt nnb (c)ie werben ben (c)pnren ber (R)tin1n1nngen, 111 Innen MB 931119 gefcf;rieben ift, 351e 9tacbficbt nicht (...) verfagen. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

Tato studie pojednává o rané fázi mikroskopického zkoumání přírody, které ve svém díle Micrographia představil Robert Hooke. Vzhledem k obsáhlosti díla se zaměřuje na pasáže, které Hooke věnoval výzkumu hmyzu. Předmětem analýzy je především metodologie Hookova výzkumu: způsob, jakým tento experimentátor využíval mikroskop ke zkoumání mravenců, much, komárů a jiného hmyzu. Dále je pozornost věnována způsobu, jakým Hooke představoval výsledky svého pozorování, tedy popisům a ilustracím hmyzu. A konečně, příspěvek se také pokouší vyložit vybrané záznamy mikroskopických pozorování v Micrographii a (...) objasnit jejich vazbu na filosofickou a náboženskou interpretaci přírody sedmnáctého století. (shrink)

Academic dishonesty among students is not confined to the dynamics of the classrooms in which it occurs. The institution has a major role in fostering academic integrity. Ways that institutions can have a significant impact on attitudes toward and knowledge about academic integrity as well as reducing the incidence of academic dishonesty are described. These include the content of an effective academic honesty policy, campus-wide programs designed to foster integrity, and the development of a campus-wide ethos that encourages integrity.

The doctrine of karma and rebirth is often praised for its ability to offer a successful solution to the Problem of Evil. This essay evaluates such a claim by considering whether the doctrine can function as a systematic theodicy, as an explanation of all human suffering in terms of wrongs done in either this or past lives. This purported answer to the Problem of Evil must face a series of objections, including the problem of anylackofmemoryofpastlives,the lack of proportionality between wrongdoing (...) and the observed suffering in the world, the problem of infinite regress of explanation, and the problem of compatibility of free will with karmic determinism. These objections, either separately or taken together, provide sufficient reason to doubt whether the doctrine of karma and rebirth can in fact provide a satisfactory theodicy. (shrink)

Authentic objects are those that have a historical link to a person, event, time, or place of some significance. The current study examines everyday beliefs about authentic objects, with three primary goals: to determine the scope of adults' evaluation of authentic objects, to examine such evaluation in two distinct cultural settings, and to determine whether a person's attachment history predicts evaluation of authentic objects. We found that college students in the UK and the USA consistently evaluate a broad range of (...) authentic items as more valuable than matched control objects, more desirable to keep, and more desirable to touch, though only non-personal authentic items were judged to be more appropriate for display in a museum. These patterns were remarkably similar across the two cultural contexts. Additionally, those who had an attachment object as a child evaluated objects more favorably, and in particular judged authentic objects to be more valuable. Altogether, these results demonstrate broad endorsement of "positive contagion" among college-educated adults. (shrink)

R.I.G. Hughes presents a series of eight philosophical essays on the theoretical practices of physics. The first two essays examine these practices as they appear in physicists' treatises (e.g. Newton's Principia and Opticks ) and journal articles (by Einstein, Bohm and Pines, Aharonov and Bohm). By treating these publications as texts, Hughes casts the philosopher of science in the role of critic. This premise guides the following 6 essays which deal with various concerns of philosophy of physics such as laws, (...) disunities, models and representation, computer simulation, explanation, and the discourse of physics. (shrink)

Review of Joel Faflak. Romantic Psychoanalysis: The Burden of the Mystery. Albany: State University of New York Press, 2008. 333 pages; paper $29.95. ISBN 978-0-7914-7269-0.

When I was a 7 months pregnant medical student, an attending surgeon asked me to which specialty I would be applying. When I replied that I was hoping to match in general surgery, he touched my pregnant abdomen and said, “Not with that you’re not.” I am not alone. Gender bias and discrimination have been shown to negatively impact women surgeons throughout their careers and deter women from even applying in surgical fields.1 Bias against female surgical trainees leads to less (...) operative autonomy and higher dropout rates.2 3 Once faculty, women surgeons are less likely to reach leadership roles.4 Recent studies confirm the author’s assertion that implicit biases create substantial harm. The author has undertaken an important study, conducting in-depth interviews with 46 women surgeons in Australia that identifies four distinct types of bias causing cumulative harm. In all four types of biases: Workplace factors including leave policies and mentorship. Epistemic injustices, or unfair assessments of women surgeons’ credibility by patients and colleagues. Stereotyped expectations. Objectification, implicit biases were seen. While many of the broad factors impeding women in surgery are well known, the author argues that these subtler factors, including both implicit bias and epistemic injustice, have a large impact. The …. (shrink)

Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. The current manuscript is a description (...) of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death. (shrink)

Increasing attention is paid in the social sciences and management studies to the constitution and claims of different theories, perspectives, and "paradigms." This book is one of the most respected and robust analyses of these issues. For this new paperback edition Richard Whitley--a leading figure in European business education--has written a new introduction which addresses the particular epistemological issues of business management studies.

Conley and colleagues (2023) conduct a fascinating analysis of how influential organizations in the global governance of human genome editing debate conceptualize and perform public engagement. Whi...

Emotion regulation (i.e. either up- or down-regulating affective responses to emotional stimuli) has been shown to modulate long-term emotional memory formation. Further, research has demonstrated that the emotional aspects of scenes are preferentially remembered relative to neutral aspects (known as the emotional memory trade-off effect). This trade-off is often enhanced when sleep follows learning, compared to an equivalent period of time spent awake. However, the interactive effects of sleep and emotion regulation on emotional memory are poorly understood. We presented 87 (...) participants with pictures of neutral or negative objects on neutral backgrounds paired with instructions to either increase or decrease their emotional response by altering personal relevance, or to passively view the stimuli. Following a 12 h period of sleep or wakefulness, participants were tested for their memory of objects and backgrounds separately. Although we replicated the emotional memory trade-off effect, no differences in the magnitude of the trade-off effect were observed between regulation conditions. Sleep improved all aspects of memory, but it did not preferentially benefit memory for emotional components of scenes. Irrespective of a period of sleep or wake following encoding, findings suggest emotion regulation during encoding did not influence memory for emotional items at a 12-hour delay. (shrink)

This book, which represents probably the most comprehensive discussion of the emergence of modem social science yet produced, is of far more than merely historical interest. The contributors set out to rewrite the history of the social sciences and to show the limitations of conventional conceptions of their development. These tasks they accomplish with great success and much distinction. Yet in so doing they contribute in a direct way to our understanding of the relation between social analysis and the nature (...) of human societies today. The brilliant and distinctive perspective of the papers in this collection is to demonstrate, with many specific examples, that social science and modem institutions have helped shape each other in mutual interplay. Modem systems are in some part con stituted through the reflexive incorporation of developing social science knowledge; on the other hand, the social sciences organise themselves in terms of a continuing reflection upon the evolution of those systems. Such a perspective, as Wagner and Wittrock in particular make clear, does not in any way either impugn the status of knowledge claims made within social science or destroy the independent reality of social institutions. The book questions the notion that the institutionalising of the social sciences can be understood as a process of their increasing autonomy from extemal social connections. 'Autonomy' forms a mode of legitima tion and a basis of power rather than a distinctive phenomenon as such. (shrink)

As they age, many people are afraid that they might become a burden to their families and friends. In fact, fear of being a burden is one of the most frequently cited reasons for individuals who request physician aid in dying. Why is this fear so prevalent, and what are the issues underlying this concern? I argue that perceptions of individual autonomy, dependency, and dignity all contribute to the fear of becoming a burden. However, this fear is misplaced; common conceptions (...) of these values should be re-framed and re-examined. Practices that support a more community-centered type of autonomy can be found in dependency and dignity. This paper offers some practical examples of how to address common end-of-life situations that may cause anxiety to patients who are worried about being a burden. These practices include discussing expectations, both for care and how the relationship among the participants might change, and modeling respectful caregiving behaviors. Most difficult of all, though, includes cultural and societal attitude changes so that people recognize the good in receiving care and get used to the idea that they do not need to do anything to be valuable. (shrink)

R.I.G Hughes offers the first detailed and accessible analysis of the Hilbert-space models used in quantum theory and explains why they are so successful.